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Search: Neonatal[Title] AND isolation[Title] AND augments[Title] AND social[Title] AND dominance[Title] AND altering[Title] AND actin[Title] AND dynamics[Title] AND medial[Title] AND prefrontal[Title] AND cortex[Title]

Neonatalisolationaugmentssocialdominance by alteringactindynamics in the medialprefrontalcortex.

Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

2

Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.

Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; takahast@yokohama-cu.ac.jp.

Abstract

Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent socialdominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatalisolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medialprefrontalcortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on socialdominance. Thus, neonatalisolation affects spines in the mPFC by reducing actindynamics, leading to altered social behavior later in life.

Socialisolation enhances socialdominance. (A) Schematic of the tube test. In this example, the left rat pushed the right rat out of the Plexiglas tube, and the left rat was declared the winner. (B) Captured video images from a representative match. From top to bottom, the beginning to the end of the match is sequentially indicated. (C) Results of a socialdominance tube test. Percentage of wins in the matches between socially isolated and nonisolated rats (10 matches). (D) Results of socialdominance tube test between socially isolated rats treated with RU486 and nonisolated rats treated with vehicle (12 matches). (E) Results of socialdominance tube test between socially isolated rats treated with RU486 and nonisolated rats treated with RU486 (seven matches). *P < 0.05 (χ2 test).

Socialisolation does not affect body weight and locomotion. Body weight, number of rearings, and number of line crossings in the open field. There was no significant difference among animals with (A) nonisolated and isolated (n = 9 rats nonisolated and 10 rats isolated), (B) nonisolated with vehicle and isolated with RU486 (n = 7 rats nonisolated with vehicle and 7 rats isolated with RU486), or (C) nonisolated with vector and isolated with S3A (n = 8 rats isolated with S3A and 6 rats isolated with vector). Error bars represent SEM. n.s., not statistically significant (unpaired Student’s t test).

Socialisolation does not affect locomotion in the tube. There was no significant difference among animals in nonisolated versus isolated groups in the latency of movement in the tube during eight training trials on each of two successive days (n = 25 rats nonisolated and 25 rats isolated) [repeated measures ANOVA F(1,733) = 0.874]. Error bars represent SEM.